Long-term intermolecular interactions are electrostatic in nature and can be studied now that detailed spatial structures of proteins are known. The shape of the electrostatic potential field, generated by charged amino acid residues, prosthetic groups and Alpha-helix dipoles, shows whether the charge distribution is symmetric or not. An asymmetric distribution of charge may indicate a possible site of reaction if the substrate is charged, as is the case for cytochrome c and superoxide dismutase. In order to further probe the relation between charge configuration and function, this new approach will be extended to other metallo-proteins. Since active sites of proteins form only a small part of the total surface area, juxta-position of these sites prior to complex formation would increase the efficiency of the reaction. A change in charge configuration on one of the reaction partners by chemical modification impairs the reaction by alteration of the net charge and dipole moment. The effect on the rate of reaction should be predictable if the site of modification is known. According to two recently derived equations, the totality of the charge configuration which take into account the ionic strength dependence of protein reactions should give information regarding the location of the site of reaction.